cagrilintide/semaglutide (CagriSema) / Novo Nordisk - LARVOL DELTA

Effects of glucagon-like peptide-1 analogues on hard binary outcomes for patients at increased risk of cardiovascular events: a protocol for a systematic review with network meta-analysis and Trial Sequential Analysis. (PubMed, BMJ Open) - "Semaglutide, tirzepatide and liraglutide are approved by the US Food and Drug Administration and the European Medicines Agency for the treatment of type 2 diabetes mellitus and overweight...Findings of this systematic review will be published in international peer-reviewed scientific journals. CRD42024623312."

Journal • Retrospective data • Cardiovascular • Chronic Kidney Disease • Diabetes • Metabolic Disorders • Myocardial Infarction • Nephrology • Obesity • Renal Disease • Type 2 Diabetes Mellitus

Engineered nutrient-stimulated hormonal multi-agonist for precision targeting of obesity and metabolic disorders. (PubMed, Clin Mol Hepatol) - "Tirzepatide (GLP-1/GIP dual agonist), CagriSema (GLP-1/amylin dual agonist), and retatrutide (GLP-1/GIP/glucagon triple agonist) have achieved unprecedented levels of weight loss and glycemic improvement, with certain agents also demonstrating hepatic, cardiovascular, and inflammatory benefits. Non-peptidyl oral GLP-1RAs, such as orforglipron, offer novel formulation strategies to enhance treatment accessibility and adherence...These therapies are poised to emerge as key components of precision metabolic medicine. This review article explores the mechanistic basis, pharmacological characteristics, and clinical data supporting the use of engineered NUSH-based peptide therapies for obesity and its related metabolic disorders, with particular emphasis on recent progress in the development and clinical application of dual and triple agonists."

Journal • Cardiovascular • Diabetes • Genetic Disorders • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Type 2 Diabetes Mellitus

Harnessing GLP-1 Receptor Agonists for Obesity Treatment: Prospects and Obstacles on the Horizon. (PubMed, J Obes) - "Currently, liraglutide, semaglutide, and tirzepatide are FDA-approved for obesity treatment, while other agents are used off-label...Novel agents including CagriSema and higher dose oral semaglutide are advancing through clinical trials, while pivotal trial results for orforglipron, mazdutide, retatrutide, and survodutide are anticipated to further expand the therapeutic landscape...The convergence of pharmacological innovation, digital health strategies, and equitable care initiatives is expected to revolutionize obesity therapeutics in the coming decade. Priorities for future research include sustaining long-term weight loss, establishing disease-modifying potential in nonmetabolic disorders, and addressing health equity concerns to ensure broader global benefit."

Journal • Review • Atherosclerosis • Cardiovascular • Chronic Kidney Disease • CNS Disorders • Congestive Heart Failure • Diabetes • Dyslipidemia • Genetic Disorders • Heart Failure • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Nephrology • Obesity • Renal Disease • Type 2 Diabetes Mellitus

CagriSema US sales projection: $2B in 2027 - A subscription to AlphaSense is required to access document | REPORT TITLE: “Novo Nordisk "Price declines are tough to offset with volume" (Neutral) Weston" | Author: Matthew Weston, et al | DATE: 12/04/25

Sales projection • Obesity

A Research Study to Investigate the Effects of CagriSema Compared to Placebo in People With Type 2 Diabetes and Painful Diabetic Peripheral Neuropathy (clinicaltrials.gov) - P2 | N=142 | Active, not recruiting | Sponsor: Novo Nordisk A/S | Recruiting ➔ Active, not recruiting

Enrollment closed • Diabetes • Diabetic Neuropathy • Metabolic Disorders • Pain • Peripheral Neuropathic Pain • Type 2 Diabetes Mellitus

Novo Nordisk to test next-gen obesity drug CagriSema in children (Reuters) - "The late-stage trial, set to begin in January, is expected to enroll 460 children as young as eight years across 97 test centers globally, including the U.S., China and Europe...The drug combines cagrilintide, which mimics pancreatic hormone amylin, and semaglutide, the active ingredient in Wegovy....The study will assess the main goal of change in baseline body weight after 68 weeks in participants randomly chosen to receive either CagriSema, cagrilintide, semaglutide or placebo."

New trial • Obesity

CagriSema Reduces Blood Pressure in Adults With Overweight or Obesity: REDEFINE 1. (PubMed, Hypertension) - P3 | "Fixed-dose combination of semaglutide/cagrilintide (CagriSema 2.4 mg/2.4 mg) has demonstrated significant and clinically relevant body weight reductions in adults with overweight or obesity compared with placebo. CagriSema presents clinically relevant reductions in BP across a wide range of participant subgroups, including those with resistant hypertension. URL: https://www.clinicaltrials.gov; Unique identifier: NCT05567796."

Journal • Cardiovascular • Diabetes • Genetic Disorders • Hypertension • Metabolic Disorders • Obesity

REIMAGINE 3: A Research Study to See How Much CagriSema Lowers Blood Sugar and Body Weight Compared to Placebo in People With Type 2 Diabetes Treated With Once-daily Basal Insulin With or Without Metformin (clinicaltrials.gov) - P3 | N=274 | Completed | Sponsor: Novo Nordisk A/S | Active, not recruiting ➔ Completed

Trial completion • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus • LEP • LEPR

A Research Study on How Well Cagrilintide and CagriSema Work in Children and Adolescents With Excess Body Weight (clinicaltrials.gov) - P3 | N=460 | Not yet recruiting | Sponsor: Novo Nordisk A/S

Monotherapy • New P3 trial • Genetic Disorders • Obesity

A Research Study to See if Kidney Damage in People With Chronic Kidney Disease and Type 2 Diabetes Living With Overweight or Obesity Can be Reduced by CagriSema Compared to Semaglutide, Cagrilintide and Placebo (clinicaltrials.gov) - P2 | N=626 | Completed | Sponsor: Novo Nordisk A/S | Active, not recruiting ➔ Completed

Trial completion • Chronic Kidney Disease • Diabetes • Genetic Disorders • Metabolic Disorders • Nephrology • Obesity • Renal Disease • Type 2 Diabetes Mellitus • CST3

Cagrilintide-Semaglutide in Adults with Overweight or Obesity. Reply. (PubMed, N Engl J Med) - No abstract available

Journal • Genetic Disorders • Obesity

Synthetic target trial emulation and predictive modeling of amylin-pathway therapies for obesity and type 2 diabetes. (PubMed, Metabol Open) - "Network meta-analysis integrated evidence across CagriSema, cagrilintide, and amycretin formulations...Virtual head-to-head modeling confirmed CagriSema superiority over amycretin subcutaneous at matched timepoints (posterior probability >0.95)...Synthetic target trial emulation with structured validation (leave-trial-out, posterior predictive checks, simulation-based calibration) demonstrated promising evidence for amylin-pathway development optimization. Benefit-risk frontier analysis identified an optimal 10-20 mg subcutaneous therapeutic window, and heterogeneity quantification through maximum a posteriori (MAP) predictive interval provides design-ready estimates for confirmatory trials requiring around 800-1,200 participants per arm for 90 % power."

Journal • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Amylin and the renin-angiotensin system: risk or opportunity in amylin-based therapy? (PubMed, Lancet) - "We hypothesise that amylin receptor agonists (eg, pramlintide) and dual amylin and calcitonin-receptor agonists (eg, cagrilintide), which are emerging treatments for obesity and type 2 diabetes, can activate the renin-angiotensin system (RAS) and potentially undermine the cardiorenal benefits of these therapies...To test this, we propose: (1) preclinical studies investigating amylin-RAS interactions with or without RAS blockade; (2) post-hoc analyses of phase 2/3 trials stratified by RAS inhibitor use; (3) biomarker studies monitoring renin, aldosterone, angiotensin-(1-7), and ACE2; and (4) mechanistic human studies prospectively assessing cardiovascular-kidney metabolic effects by RAS inhibitor status. These suggestions aim to determine whether RAS inhibition enhances the overall efficacy of amylin-based therapies, and whether RAS blockers should be strongly recommended in patients receiving them."

Journal • Review • Cardiovascular • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

REDEFINE 5: CagriSema in East Asian Adults With Overweight or Obesity, With or Without T2D (OBESITY WEEK 2025) - P3 | "Background: The combination of semaglutide (sema) 2.4 mg and cagrilintide 2.4 mg (CagriSema 2.4 mg/2.4 mg) has been shown to induce weight loss in adults with overweight and obesity in the REDEFINE 1 and 2 trials... CagriSema provided superior and clinically meaningful weight reduction and improvements in cardiometabolic risk factors in East Asian adults with overweight or obesity, with or without T2D, compared with sema. Safety and tolerability were comparable with other incretin-based therapies and previous trials of CagriSema."

Clinical • Diabetes • Dyslipidemia • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

CagriSema Reduces Predicted ASCVD Risk in Adults With Overweight or Obesity: The REDEFINE 1 Trial (OBESITY WEEK 2025) - P3 | "Adults (N=3417) with body mass index ≥30 kg/m2, or ≥27 kg/m2 with ≥1 obesity-related complication, without diabetes, were randomized 21:3:3:7 to receive CagriSema (n=2108), semaglutide (n=302), cagrilintide (n=302), or placebo (n=705), plus lifestyle intervention, for 68 weeks. After 68 weeks of treatment, CagriSema reduced the proportion of participants who were at intermediate–high risk of developing ASCVD within the next 10 years."

Clinical • Atherosclerosis • Cardiovascular • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity

CagriSema Reduces hsCRP in Adults With Overweight or Obesity: the REDEFINE 1 Trial (OBESITY WEEK 2025) - P3 | "Participants were randomized 21:3:3:7 to CagriSema (n=2108), semaglutide (n=302), cagrilintide (n=302), or placebo (n=705) for 68 weeks, plus lifestyle intervention... At baseline, mean (standard deviation) age was 47.0 (11.8) years and 67.6% of participants were female; 14.9% of participants were on statins, 0.5% on systemic glucocorticoids, 0.4% on colchicine, and 13.3% were current smokers... CagriSema treatment for 68 weeks appeared to reduce hsCRP across all baseline hsCRP levels, and independent of the other baseline characteristics assessed in participants with overweight or obesity. In a mediation analysis, the hsCRP reductions with CagriSema were not solely driven by weight loss. These results suggest a potential anti-inflammatory effect of CagriSema in people with overweight or obesity that may lower CV risk."

Clinical • Cardiovascular • Diabetes • Genetic Disorders • Inflammation • Metabolic Disorders • Obesity • CRP

CagriSema Reduces Blood Pressure in Adults With Overweight or Obesity: The REDEFINE 1 Trial (OBESITY WEEK 2025) - P3 | "Participants (N=3417) were randomized 21:3:3:7 to CagriSema (n=2108), semaglutide (n=302), cagrilintide (n=302), or placebo (n=705), and lifestyle intervention, for 68 weeks. CagriSema significantly reduced blood pressure in participants with overweight or obesity, irrespective of whether their baseline BMI was greater than or less than 35 kg/m2. This was associated with reduced use of antihypertensive medication in those on medication at baseline. These data reveal a marked, previously unrecognized antihypertensive benefit of CagriSema—an important advance given that hypertension remains refractory in people with obesity and is the leading driver of cardiovascular disease worldwide."

Clinical • Cardiovascular • Diabetes • Genetic Disorders • Hypertension • Metabolic Disorders • Obesity

Effect of CagriSema 2.4mg/2.4mg on Body Composition, Muscle Strength & Physical Function: REDEFINE 1 (OBESITY WEEK 2025) - " REDEFINE 1, a phase 3a, double-blind, placebo- and active-controlled study randomized 3417 participants with BMI ≥30 kg/m2, or ≥27 kg/m2 with ≥1 obesity-related complication, in a 21:3:3:7 ratio to once-weekly subcutaneous CagriSema 2.4 mg/2.4 mg, semaglutide 2.4 mg, cagrilintide 2.4 mg, or placebo, plus lifestyle intervention for 68 weeks. In REDEFINE 1, the improvements in fat-to-lean soft tissue mass ratio were associated with improvements in physical function, and there was no decline in muscle strength compared with placebo."

Genetic Disorders • Obesity • Sarcopenia

CagriSema and Achievement of BMI and Waist-to-Height Ratio Treatment Targets: REDEFINE 1 (OBESITY WEEK 2025) - " Participants (BMI ≥30 kg/m2, or ≥27 kg/m2 with ≥1 ORC) were randomized in a double-blind manner to CagriSema, semaglutide, cagrilintide or placebo, as add-on to lifestyle intervention, for 68 weeks. In this analysis of REDEFINE 1, a greater proportion of participants treated with CagriSema achieved clinically relevant treatment targets vs comparators. These data highlight the link between new targets in the clinical management of obesity, achieved by nearly a third of participants exposed to CagriSema, and normalization of cardiometabolic parameters."

Genetic Disorders • Obesity • CRP

Novo Nordisk’s CagriSema was associated with significant reduction in blood pressure and showed anti-inflammatory effects while reducing the proportion of patients at risk of developing heart disease over time in new analyses at ObesityWeek (Novo Nordisk Press Release) - "A post hoc analysis of REDEFINE 1 demonstrated a 10.9 mmHg reduction in systolic blood pressure with investigational CagriSema (2.4 mg/2.4 mg), allowing 40% of people on blood pressure medications to reduce or stop their medication. CagriSema treatment demonstrated a nearly 70% reduction in a key inflammatory marker associated with increased cardiovascular risk. Data showed that fewer people on CagriSema were at intermediate-to-high risk of developing atherosclerotic cardiovascular disease (ASCVD) within the next 10 years."

P3 data • Obesity

A Research Study to See How Well CagriSema Compared to Tirzepatide Helps People With Obesity Lose Weight (clinicaltrials.gov) - P3 | N=809 | Active, not recruiting | Sponsor: Novo Nordisk A/S | Trial primary completion date: Aug 2025 ➔ Dec 2025

Trial primary completion date • Genetic Disorders • Obesity

Novo Nordisk to present new data in oral semaglutide 25 mg (Wegovy in a pill) and obesity pipeline at ObesityWeek 2025 (PRNewswire) - "New data from OASIS 4 on oral semaglutide 25 mg to reveal insights on cardiometabolic health among adults with obesity or overweight; Additional trial insights into impact on ability to do everyday activities and women's health among adults with obesity or overweight will also be shared, New CagriSema data from REDEFINE to be presented, highlighting innovative pipeline"

Clinical data • Obesity

A Research Study to Look Into the Long-term Effect on Weight Loss of CagriSema in People With Obesity (clinicaltrials.gov) - P3 | N=400 | Active, not recruiting | Sponsor: Novo Nordisk A/S | Recruiting ➔ Active, not recruiting

Enrollment closed • Genetic Disorders • Obesity

Novel GLP-1-Based Medications for Type 2 Diabetes and Obesity. (PubMed, Endocr Rev) - "Maridebart cafraglutide, combining GLP-1R agonism with GIPR antagonism, exemplifies this innovative approach. Glucagon co-agonists like survodutide and mazdutide have demonstrated significant weight loss and improved glycemic control. Amylin-based agents, including CagriSema (cagrilintide + semaglutide) and amycretin, enhance satiety and glycemic outcomes through complementary actions. Further innovation is seen in triple agonists such as retatrutide, which targets GIP, GLP-1, and glucagon receptors to amplify metabolic effects. Meanwhile, the emergence of orally active small-molecule GLP-1 receptor agonists like danuglipron and orforglipron, which are resistant to enzymatic degradation, marks a major advance in patient-friendly drug delivery. This review explores the mechanisms, clinical development, and therapeutic potential of these novel agents, excluding already approved drugs like liraglutide, semaglutide, and tirzepatide. We highlight how multi-receptor agonists..."

Journal • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

A Study to See How Metabolism is Influenced by Weight Loss Due to Intervention With Cagrilintide and Semaglutide Compared to Diet (clinicaltrials.gov) - P1 | N=80 | Recruiting | Sponsor: Novo Nordisk A/S | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders • Obesity